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“Teaching old dogs new tricks”:targeting neural extracellular matrix for normal and pathological aging-related cognitive decline

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Neural Regeneration Research 2019年第4期14卷 578-581页

作者： adam d.richard Xiao-Hong Lu department of Pharmacology Toxicology and Neuroscience Louisiana State University Health Sciences Center

Cognitive decline is a feature of normal and pathological aging. As the proportion of the global aged population continues to grow, it is imperative to understand the molecular and cellular substrates of cognitive aging for therapeutic discovery. This review focuses on the critical role of neural extracellular matrix in the regulation of neuroplasticity underlying learning and memory in another under-investigated "critical period": the aging process. The fascinating ideas of neural extracellular matrix forming a synaptic cradle in the tetrapartite synapse and possibly serving as a substrate for storage of very long-term memories will be introduced. We emphasize the distinct functional roles of diffusive neural extracellular matrix and perineuronal nets and the advantage of the coexistence of two structures for the adaptation to the ever-changing external and internal environments. Our study of striatal neural extracellular matrix supports the idea that chondroitin sulfate proteoglycan-associated extracellular matrix is restrictive on synaptic neuroplasticity, which plays important functional and pathogenic roles in early postnatal synaptic consolidation and aging-related cognitive decline. Therefore, the chondroitin sulfate proteoglycan-associated neural extracellular matrix can be targeted for normal and pathological aging. Future studies should focus on the cell-type specificity of neural extracellular matrix to identify the endogenous, druggable targets to restore juvenile neuroplasticity and confer a therapeutic benefit to neural circuits affected by aging.

关键词： aging cognitive decline neural extracellular matrix tetrapartite synapse long-term memory storage therapeutic targeting striatum chondroitin sulfate proteoglycan

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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： daniel adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (Ad),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of Ad and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

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Monte Carlo sampling for error propagation in linear regression and applications in isochron geochronology

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Science Bulletin 2019年第3期64卷 189-197页

作者： Yang Li Shuang Zhang richard Hobbs Camila Caiado adam d.Sproson david Selby Alan d.Rooney State Key Laboratory of Lithospheric Evolution Institute of Geology and Geophysics Chinese Academy of Sciences department of Earth Sciences Durham University department of Geology and Geophysics Yale University department of Mathematical Sciences Durham University Atmosphere and Ocean Research Institute The University of Tokyo

Geochronology is essential for understanding Earth's history. The availability of precise and accurate isotopic data is increasing; hence it is crucial to develop transparent and accessible data reduction techniques and tools to transform raw mass spectrometry data into robust chronological data. Here we present a Monte Carlo sampling approach to fully propagate uncertainties from linear regressions for isochron dating. Our new approach makes no prior assumption about the causes of variability in the derived chronological results and propagates uncertainties from both experimental measurements(analytical uncertainties) and underlying assumptions(model uncertainties) into the final age *** synthetic examples, we find that although the estimates of the slope and y-intercept(hence age and initial isotopic ratios) are comparable between the Monte Carlo method and the benchmark‘‘Isoplot" algorithm, uncertainties from the later could be underestimated by up to 60%, which are likely due to an incomplete propagation of model uncertainties. An additional advantage of the new method is its ability to integrate with geological information to yield refined chronological constraints. The new method presented here is specifically designed to fully propagate errors in geochronological applications involves linear regressions such as Rb-Sr, Sm-Nd, Re-Os, Pt-Os, Lu-Hf, U-Pb(with discordant points),Pb-Pb and Ar-Ar.

关键词： Linear regression Isochron Geochronology Uncertainty propagation Monte Carlo Isoplot

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Prevalence of Barrett's esophagus in patients with moderate to severe erosive esophagitis

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World Journal of Gastroenterology 2008年第22期14卷 3518-3522页

作者： Nooman Gilani richard d Gerkin Francisco C Ramirez Shahina Hakim adam C Randolph department of Medicine and Research Section of Gastroenterology Carl. T. Hayden Veterans Administration Medical Center Phoenix Arizona 85012 United States

AIM: To investigate the proportion of patients with moderate-severe erosive esophagitis (EE) who will have Barrett's esophagus (BE) after healing of inflammation. METHOdS: Patients with EE of Los Angeles (LA) class B, C and d who underwent follow-up endoscopy documenting complete mucosal healing. RESULTS: A total of 86/169 patients were suspected of having BE (38 before healing and 48 after healing of EE) and, 46/86 eventually had the histological confirmation. At index esophago-gastro-duodenoscopy (EGd), BE was suspected in 38/169 (22%), and ultimately, histologically confirmed in 20 of these. In 11 patients where biopsies were performed in the presence of inflammation, BE was detected in 2 and missed in 5 (including 2 dysplasias). In 131/169 patients (77.5%), BE was not suspected at index EGd. After healing of EE though, 48 patients had suspicion of BE who underwent biopsies, and in 26 of these histology was positive for BE. The length of inflammation had a linear correlation with the length of BE (P = 0.01). Out of multiple variables to predict BE, only the suspicion at index endoscopy was statistically significant (P = 0.01). CONCLUSION: BE was seen in 46/169 (27%) patients with EE of LA class B, C and d. The length of EE can predict the length of underlying BE *** when suspected, BE and associated dysplasia can be missed in the presence of inflammation; therefore, repeat evaluation should be considered after complete healing of esophagitis.

关键词： Erosive Esophagitis Barrett's Prevalence of Barrett's Gastroesophageal reflux

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Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng adam M.R.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne Moore Jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

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Genetic interactions and modifi er genes in Hirschsprung's disease

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World Journal of Gastroenterology 2011年第45期17卷 4937-4944页

作者： adam S Wallace richard B Anderson department of Anatomy and Cell Biology University of Melbourne

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

关键词： Neural crest Enteric nervous system Hirschsprung’s disease Aganglionosis Modif ier genes

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Adipose derived stem cells and nerve regeneration

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Neural Regeneration Research 2014年第14期9卷 1341-1346页

作者： Alessandro Faroni richard JP Smith adam J Reid Blond McIndoe Laboratories Institute of Inflammation and RepairUniversity of ManchesterManchesterUK department of Plastic Surgery & Burns University Hospital of South Manchester ManchesterUK

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.

关键词： peripheral nerve injury adipose derived stem cells nerve guidance tubes bioengineerednerve graft axonal regeneration Schwann cell cell therapy nerve repair

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Phylogenetic status of Pneumocystis from corticosteroid-treated gerbils

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Science China(Life Sciences) 2010年第10期53卷 1239-1246页

作者： ROdNEY d adam department of Medicine and Immunobiology University of Arizona College of Medicine

Pneumocystis spp. infect the lungs of multiple mammalian species and cause disease in immunosuppressed individuals. The Pneumocystis isolates that have been studied to date fall into two major clades, those from primates and those from rodents. Within each of these clades, different species have been described on the basis of host specificity and differences in sequence and morphology. Here, we demonstrate that dexamethasone immunosuppression consistently results in histologically apparent lung infection in gerbils (28/35 animals). Sequence analysis of the 18S, 5.8S and internal transcribed spacer regions of the rdNA and a portion of the mitochondrial large subunit rdNA demonstrated that this gerbil Pneumocystis is grouped with other rodent Pneumocystis spp., but is distinct from them. Our results suggest that gerbil Pneumocystis differs sufficiently from Pneumocystis species found in other rodents to be considered a separate species.

关键词： 5.8S rRNA gene gerbil internal transcribed spacers (ITS) mitochondrial large subunit (mtLS) rRNA gene 18S rRNA gene Pneumocystis

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determining minimum sample size for the conditioned Latin hypercube sampling algorithm

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Pedosphere 2024年第3期34卷 530-539页

作者： daniel d.SAURETTE Asim BISWAS richard J.HECK adam W.GILLESPIE Aaron A.BERG School of Environmental Sciences University of Guelph50 Stone Rd EastGuelph ON N1G 2W1(Canada) Ontario Ministry of Agriculture Food and Rural Affairs1 Stone Rd WestGuelph ON N1G 2Y4(Canada) Geography Environment&GeomaticsUniversity of Guelph50 Stone Rd EastGuelph ON N1G 2W1(Canada)

In digital soil mapping(dSM),a fundamental assumption is that the spatial variability of the target variable can be explained by the predictors or environmental *** to adequately sample the predictors have been well documented,with the conditioned Latin hypercube sampling(cLHS)algorithm receiving the most attention in the dSM *** advances in sampling design,a critical gap remains in determining the number of samples required for dSM *** propose a simple workflow and function coded in R language to determine the minimum sample size for the cLHS algorithm based on histograms of the predictor variables using the Freedman-diaconis rule for determining optimal bin *** preprocessing was included to correct for multimodal and non-normally distributed data,as these can affect sample size determination from the *** on a user-selected quantile range(QR)for the sample plan,the densities of the histogram bins at the upper and lower bounds of the QR were used as a scaling factor to determine minimum sample *** technique was applied to a field-scale set of environmental covariates for a well-sampled agricultural study site near Guelph,Ontario,Canada,and tested across a range of *** results showed increasing minimum sample size with an increase in the QR *** sample size increased from 44 to 83 when the QR increased from 50% to 95% and then increased exponentially to 194 for the 99%*** technique provides an estimate of minimum sample size that can be used as an input to the cLHS algorithm.

关键词： bin width digital soil mapping normal distribution quantile range sampling design

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Effects of symmetric and asymmetric salt conditions on a selective solid-state nanopore assay

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Nano Research 2022年第11期15卷 9936-9942页

作者： Ian d.Wadsworth adam R.Hall Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences Wake Forest School of MedicineWinston-SalemNC 27101USA Comprehensive Cancer Center Wake Forest School of MedicineWinston-SalemNC 27157USA

Conventional solid-state nanopore measurements sense all translocating entities,necessitating meticulous analysis to differentiate target *** address this,we have established a selective assay with the platform that has shown utility in quantifying several nucleic acid ***,limited detection efficiency and intrinsic noise have so far limited assay resolution to 10 *** in this value require manipulation of translocation ***,we report the effects of NaCl conditions on assay *** first investigate symmetric conditions,finding sensitivity increases with salt concentration but selectivity is maximized at 1.0 M *** then probe asymmetric conditions,showing a remarkable impact on assay sensitivity and selectivity when measurement buffer NaCl concentration in the reservoir with the translocating molecules is low and the opposite reservoir is *** optimum conditions,we demonstrate detection of target biomolecules down to a concentration of 100 pM which is an improvement of 2 orders of magnitude over past results.

关键词： solid-state nanopores biomarkers amplification-free detection salt gradient nucleic acids

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